MCAT Biochemistry Review

Chapter 12: Bioenergetics and Regulation of Metabolism

12.6 Tissue-Specific Metabolism

Tissues have evolved so that their metabolic needs are met in a way corresponding to their form and function. The major sites of metabolic activity in the body are the liver, skeletal and cardiac muscles, brain, and adipocytes. Connective tissue and epithelial cells do not make major contributions to the consumption of energy. Remember though, that epithelial cells are the primary secretory cells, so they are involved in the regulation of metabolism. We have already discussed how the body operates under different nutritional conditions. The organ-specific patterns of fuel utilization in the well-fed and fasting states are summarized in Table 12.2.





Glucose and amino acids

Fatty acids

Resting skeletal muscle


Fatty acids, ketones

Cardiac muscle

Fatty acids

Fatty acids, ketones

Adipose tissue


Fatty acids



Glucose (ketones in prolonged fast)

Red blood cells



Table 12.2. Preferred Fuels in the Well-Fed and Fasting States


Two major roles of the liver in fuel metabolism are to maintain a constant level of blood glucose under a wide range of conditions and to synthesize ketones when excess fatty acids are being oxidized. After a meal, glucose concentration in the portal blood is elevated. The liver extracts excess glucose and uses it to replenish its glycogen stores. Any glucose remaining in the liver is then converted to acetyl-CoA and used for fatty acid synthesis. The increase in insulin after a meal stimulates both glycogen synthesis and fatty acid synthesis in the liver. The fatty acids are converted to triacylglycerols and released into the blood as very-low-density lipoproteins (VLDLs). In the well-fed state, the liver derives most of its energy from the oxidation of excess amino acids. Between meals and during prolonged fasts, the liver releases glucose into the blood. The increase in glucagon during fasting promotes both glycogen degradation and gluconeogenesis. Lactate from anaerobic metabolism, glycerol from triacylglycerols, and amino acids provide carbon skeletons for glucose synthesis.


After a meal, elevated insulin levels stimulate glucose uptake by adipose tissue. Insulin also triggers fatty acid release from VLDLs and chylomicrons (which carry triacylglycerols absorbed from the gut). Lipoprotein lipase, an enzyme found in the capillary bed of adipose tissue, is also induced by insulin. The fatty acids that are released from lipoproteins are taken up by adipose tissue and re-esterified to triacylglycerols for storage. The glycerol phosphate required for triacylglycerol synthesis comes from glucose that is metabolized in adipocytes as an alternative product of glycolysis.Insulin can also effectively suppress the release of fatty acids from adipose tissue. During the fasting state, decreased levels of insulin and increased epinephrine activate hormone-sensitive lipase in fat cells, allowing fatty acids to be released into the circulation.


Resting Muscle

The major fuels of skeletal muscle are glucose and fatty acids. Because of its enormous bulk, skeletal muscle is the body's major consumer of fuel. After a meal, insulin promotes glucose uptake in skeletal muscle, which replenishes glycogen stores and amino acids used for protein synthesis. Both excess glucose and amino acids can also be oxidized for energy. In the fasting state, resting muscle uses fatty acids derived from free fatty acids circulating in the bloodstream. Ketone bodies may also be used if the fasting state is prolonged.

Active Muscle

The primary fuel used to support muscle contraction depends on the magnitude and duration of exercise as well as the major fibers involved. A very short-lived source of energy (2–7 seconds) comes from creatine phosphate, which transfers a phosphate group to ADP to form ATP. Skeletal muscle has stores of both glycogen and some triacylglycerols. Blood glucose and free fatty acids may also be used. Short bursts of high-intensity exercise are also supported by anaerobic glycolysis drawing on stored muscle glycogen. During moderately high-intensity, continuous exercise, oxidation of glucose and fatty acids are both important, but after 1 to 3 hours of continuous exercise at this level, muscle glycogen stores become depleted, and the intensity of exercise declines to a rate that can be supported by oxidation of fatty acids.


Fast-twitch muscle fibers have a high capacity for anaerobic glycolysis but are quick to fatigue. They are involved primarily in short-term, high-intensity exercise. Slow-twitch muscle fibers in arm and leg muscles are well vascularized and primarily oxidative. They are used during prolonged, low-to-moderate intensity exercise and resist fatigue. Slow-twitch fibers and the number of their mitochondria increase dramatically in trained endurance athletes. The musculoskeletal system is discussed in Chapter 11 of MCAT Biology Review.


Unlike other tissues of the body, cardiac myocytes prefer fatty acids as their major fuel, even in the well-fed state. When ketones are present during prolonged fasting, they can also be used. Thus, not surprisingly, cardiac myocytes most closely parallel skeletal muscle during extended periods of exercise. In patients with cardiac hypertrophy (thickening of the heart muscle), this situation reverses to some extent. In a failing heart, glucose oxidation increases and β-oxidation falls.


Although the brain represents only 2 percent of total body weight, it obtains 15 percent of the cardiac output, uses 20 percent of total O2, and consumes 25 percent of the total glucose, the brain's primary fuel. Blood glucose levels are tightly regulated to maintain a sufficient glucose supply for the brain (and sufficient concentration while studying). Normal function depends on a continuous glucose supply from the bloodstream. In hypoglycemic conditions  hypothalamic centers in the brain sense a fall in blood glucose level, and the release of glucagon and epinephrine is triggered. Fatty acids cannot cross the blood–brain barrier and are therefore not used at all as an energy source. Between meals, the brain relies on blood glucose supplied by either hepatic glycogenolysis or gluconeogenesis. Only during prolonged fasting does the brain gain the capacity to use ketone bodies for energy, and even then, the ketone bodies only supply approximately two-thirds of the fuel; the remainder is glucose.

MCAT Concept Check 12.6:

Before you move on, assess your understanding of the material with these questions.

1.    What is the preferred fuel for most cells in the well-fed state? What is the exception and its preferred fuel?

·        Preferred fuel: 

·        Exception:  Preferred fuel: 

2.    What organ consumes the greatest amount of glucose relative to its percentage of body mass?

3.    Describe the major metabolic functions of the liver.